Blood vessels are the parts of the circulatory system responsible for transporting oxygen-rich red blood cells, nutrients, and immune cells throughout the body, with defects in these transport systems shown to cause a variety of life-threatening diseases. Therefore, a way to generate blood vessels via angiogenesis is critical for meeting tissue oxygen demands. Now, a study from researchers at Osaka University identifies adult vascular endothelial stem cells (VESCs) capable of generating fully functional blood vessels. The team states the VESCs expand and regenerate entire vasculature structures, supporting the existence of an endothelial hierarchy within blood vessels. The study is published in the journal Cell Stem Cell.
Previous studies indicate the existence of tissue-resident stem cells in regards to blood vessels has been intensely debated. Recent studies from the lab identified a population of endothelial cells (ECs), isolated from the innermost layer of blood vessels, with properties resembling those of stem cells. The researchers identified a glycoprotein, called CD157, expressed in the small fraction of the EC population. The key characteristic of stem cells is their ability to regenerate themselves, with the group hypothesizing CD157-positive ECs could possibly form new blood vessels. The current study tests this theory on mice with damaged blood vessels supplying blood to the hepatic artery by injecting them with CD157-positive ECs isolated from the liver.
The current study shows a month after transplantation, the CD157-enriched cells generated fully functional portal veins, portal venules, sinusoids, hepatic venules, and arteries, essentially, every type of blood vessel found in a healthy liver. Results show even the injection of a single cell is enough to reconstitute hepatic blood vessels. Data findings show a year later, the cells continue to replenish normal blood vessel tissue in the liver, mimicking functioning, native stem cells.
Data findings show when VESCs collected from healthy mice are injected into mice with hemophilia A, the cells begin generating new liver blood vessels. The group states the therapeutic potential of these cells does not appear to be limited to liver defects, with VESCs from muscle tissue successfully used to treat mice with limb ischemia, where a lack of oxygenated blood can lead to tissue damage and foot necrosis. They conclude their study potentially represents a turning point in cell-based therapies for blood vessel disorders.
The team surmises their findings show CD157-positive vascular endothelial stem cells give rise to a hierarchy of cell types able to repair blood vessels and maintain regular blood vessel architecture. For the future, the researchers state they believe their findings represent an entirely new way of thinking about how blood vessels are formed and, ultimately, how stem cells can be used to treat disorders related to blood vessel malfunction.
Source: Osaka University
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